This proposal represents a continuation and major expansion of HL 23560, Platelet Aggregation in Diabetic Mice. We will continue to study platelet aggregation in cerebral microvessels of diabetics following vascular injury. We will now extend our study to include analysis of changes in vessel diameter that occur after injury and to changes in vascular reactivity of uninjured vessels. The response to injury, that is platelet aggregation and altered diameter in diabetics, will be compared with that in normals, as will vascular reactivity in diabetics. In addition our in vivo studies are expanded so that cerebrovascular responses will be compared with microvascular responses in mesentery. Studies will be carried out both in animals with juvenile and adult onset of diabetes rather than with a mixed group as before. In vivo aggregaton will be related to red cell velocity values (shear rates) determined on-line and "normalized" to take differences in velocity into account. Studies of plasma lipid fractions, insulin levels and the platelet insulin receptor are added as are studies of prostaglandin levels and synthesis. It is hoped that the information obtained from the latter studies will correlated with and/or explain in vivo observations. In a further effort to explain in vivo data, extensive in vitro studies of aggregation, using platelet rich plasma and washed platelets, have been added to the protocol. These in vitro studies will also include investigations of the platelet release reaction in diabeties compared with non diagetics.